Functional and inhibitory studies on cystathionine-Gamma-Lyase (CSE)

Abstract

In recent years, increased interest has been directed towards hydrogen sulfide (H2S) as a third gasotransmitter and its role in various neurodegenerative and cardiovascular diseases. Cystathionine-gamma-lyase is one of the two enzymes believed to be responsible for the endogenous production of H2S. In this work, we aimed to develop inhibitors of CSE towards H2S production, as well as gain a better understanding on the function of the enzyme. To achieve this, an expression system for the human CSE enzyme was developed to enable a more reliable method of screening of inhibitors. Various forms of the enzyme were also crystallized and their structures determined via X-ray crystallography. The mechanism of H2S production was also explored via site-directed mutagenesis and kinetic studies. A polyclonal rabbit antibody that is specific towards human CSE was also developed so as to allow for future functional studies on the enzyme.